TRH and histidyl-proline diketopiperazine inhibit cholesterol synthesis in dog intestine.
Low concentrations of thyrotropin-releasing hormone and one of its metabolites, histidyl-proline diketopiperazine, are shown to have an inhibitory effect on the activation of 3-hydroxy-3-methylglutaryl coenzyme A reductase which occurs during organ culture of canine intestinal mucosa. Somatostatin and vasoactive intestinal polypeptide, in contrast, are shown to have no effect. Thyrotropin-releasing hormone, recently shown to be present in gut mucosa, may be a physiological regulator of intestinal cholesterol synthesis. Histidyl-proline diketopiperazine, an active metabolite of the hormone, is possibly the active agent since its inhibitory effect was observed at a concentration as low as 10(-12) M. These observations demonstrate an effect on intestinal metabolism by a neurotransmitter-like hormone at potentially physiologic concentrations.
D000818:Animals; D002784:Cholesterol / Q000096:biosynthesis*; D004285:Dogs; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D007082:Ileum / Q000187:drug effects / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D009924:Organ Culture Techniques; D010456:Peptides, Cyclic / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology*
D010456:Peptides, Cyclic; D010879:Piperazines; D013973:Thyrotropin-Releasing Hormone; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; C015924:histidyl-proline diketopiperazine